An experimental therapy for opioid withdrawal syndrome
dc.contributor.committeeMember | Malin, David H. | |
dc.contributor.committeeMember | Moreno, Georgina | |
dc.creator | Reed, Yvonne | |
dc.creator.orcid | 0009-0000-6547-1565 | |
dc.date.accessioned | 2024-03-25T16:37:01Z | |
dc.date.available | 2024-03-25T16:37:01Z | |
dc.date.created | 2023-12 | |
dc.date.issued | 2023-12-04 | |
dc.date.submitted | December 2023 | |
dc.date.updated | 2024-03-25T16:37:02Z | |
dc.description.abstract | The ongoing opioid crisis in the United States needs alternative therapeutics. To explore the role of the 5-HT2A serotonin receptor in opioid physical dependence and withdrawal syndrome, morphine dependent rats were treated with pimavanserin, a highly selective 5-HT2A inverse agonist in current medical use. In experiment 1, rats were rendered morphine-dependent after seven days of continuous infusion at 0.6 mg/kg/hr. On the seventh day, morphine infusion ceased, and a day later, rats were injected with either 0.3 or 1.0 mg/kg pimavanserin or saline. A non-morphine dependent saline-infused control group received only saline. One hour post injection, rats were observed under blind conditions for somatically expressed behavioral withdrawal signs utilizing a validated observation checklist. Compared to morphine dependent/saline-injected rats, the non-dependent rats and both morphine-dependent pimavanserin dose groups exhibited significantly reduced withdrawal signs, p < .001, based on Tukey’s HSD test for non-independent pairwise comparisons. The higher pimavanserin dose (1.0 mg/kg) fully reversed the effect of morphine infusion on withdrawal signs, while the lower dose (0.3 mg/kg) largely reversed it. In experiment 2, utilizing only non-dependent/salineinfused rats, pimavanserin showed no significant effect on overall withdrawal signs. Given pimavanserin’s high selectivity for the 5-HT2A serotonin receptor, these findings indicate that the activity of this receptor plays a role in opioid physical dependence. These results suggest the need for further research on pimavanserin as a novel therapeutic for managing the aversive withdrawal symptoms associated with opioid withdrawal syndrome. | |
dc.format.mimetype | application/pdf | |
dc.identifier.uri | https://hdl.handle.net/10657.1/4932 | |
dc.language.iso | en | |
dc.subject | 5-HT2A receptor | |
dc.subject | opiate dependence | |
dc.subject | opioid withdrawal | |
dc.subject | morphine dependence | |
dc.subject | morphine withdrawal | |
dc.subject | pimavanserin | |
dc.subject | 5-HT2A inverse agonist | |
dc.subject | rat | |
dc.title | An experimental therapy for opioid withdrawal syndrome | |
dc.type | Thesis | |
dc.type.material | text | |
thesis.degree.grantor | University of Houston-Clear Lake | |
thesis.degree.level | Masters | |
thesis.degree.name | Master of Science |
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